Elevated FBXL6 expression in hepatocytes activates VRK2-transketolase-ROS-mTOR-mediated immune evasion and liver cancer metastasis in mice

Zhang Jie,Lin Xiao-Tong,Yu Hong-Qiang,Fang Lei,Wu Di,Luo Yuan-Deng,Zhang Yu-Jun,Xie Chuan-Ming 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Metastatic hepatocellular carcinoma (HCC) is the most lethal malignancy and lacks effective treatment. FBXL6 is overexpressed in human hepatocellular carcinoma (HCC), but whether this change drives liver tumorigenesis and lung metastasis in vivo remains unknown. In this study, we aimed to identify FBXL6 (F-Box and Leucine Rich Repeat Protein 6) as a key driver of HCC metastasis and to provide a new paradigm for HCC therapy. We found that elevated FBXL6 expression in hepatocytes drove HCC lung metastasis and was a much stronger driver than Kras mutation (KrasG12D/+;Alb-Cre), p53 haploinsufficiency (p53+/-) or Tsc1 loss (Tsc1fl/fl;Alb-Cre). Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation. Activated TKT further increased PD-L1 and VRK2 expression via the ROS-mTOR axis, leading to immune evasion and HCC metastasis. Targeting or knockdown of TKT significantly blocked FBXL6-driven immune evasion and HCC metastasis in vitro and in vivo. Notably, the level of active TKT (p-Thr287 TKT) was increased and was positively correlated with the FBXL6 and VRK2 expression levels in HCC patients. Our work provides novel mechanistic insights into FBXL6-driven HCC metastasis and suggests that targeting the TKT-ROS-mTOR-PD-L1/VRK2 axis is a new paradigm for treating patients with metastatic HCC with high FBXL6 expression.

Physical properties and chemical composition of the cores in the California molecular cloud

Zhang, Guo-Yin,Xu, Jin-Long,Vasyunin, A. I.,Semenov, D. A.,Wang, Jun-Jie,Dib, Sami,Liu, Tie,Liu, Sheng-Yuan,Zhang, Chuan-Peng,Liu, Xiao-Lan,Wang, Ke,Li, Di,Wu, Zhong-Zu,Yuan, Jing-Hua,Li, Da-Lei,Gao, Springer-Verlag 2018 Astronomy and astrophysics Vol.620 No.-

<P><I>Aims.</I> We aim to reveal the physical properties and chemical composition of the cores in the California molecular cloud (CMC), so as to better understand the initial conditions of star formation.</P><P><I>Methods.</I> We made a high-resolution column density map (18.2′′) with <I>Herschel</I> data, and extracted a complete sample of the cores in the CMC with the fellwalker algorithm. We performed new single-pointing observations of molecular lines near 90 GHz with the IRAM 30m telescope along the main filament of the CMC. In addition, we also performed a numerical modeling of chemical evolution for the cores under the physical conditions.</P><P><I>Results.</I> We extracted 300 cores, of which 33 are protostellar and 267 are starless cores. About 51% (137 of 267) of the starless cores are prestellar cores. Three cores have the potential to evolve into high-mass stars. The prestellar core mass function (CMF) can be well fit by a log-normal form. The high-mass end of the prestellar CMF shows a power-law form with an index <I>α</I> = −0.9 ± 0.1 that is shallower than that of the Galactic field stellar mass function. Combining the mass transformation efficiency (<I>ε</I>) from the prestellar core to the star of 15 ± 1% and the core formation efficiency (CFE) of 5.5%, we suggest an overall star formation efficiency of about 1% in the CMC. In the single-pointing observations with the IRAM 30m telescope, we find that 6 cores show blue-skewed profile, while 4 cores show red-skewed profile. [HCO<SUP>+</SUP>]/[HNC] and [HCO<SUP>+</SUP>]/[N2H<SUP>+</SUP>] in protostellar cores are higher than those in prestellar cores; this can be used as chemical clocks. The best-fit chemical age of the cores with line observations is ~5 × 10<SUP>4</SUP> yr.</P>

Characterization and Antioxidant Activity of Released Exopolysaccharide from Potential Probiotic Leuconostoc mesenteroides LM187

( Qing Zhang ),( Jie Wang ),( Qing Sun ),( Shu-ming Zhang ),( Xiang-yang Sun ),( Chan-yuan Li ),( Miao-xin Zheng ),( Wen-liang Xiang ),( Jie Tang ) 한국미생물 · 생명공학회 2021 Journal of microbiology and biotechnology Vol.31 No.8

A released exopolysaccharide (rEPS)-producing strain (LM187) with good acid resistance, bile salt resistance, and cholesterol-lowering properties was isolated from Sichuan paocai and identified as Leuconostoc mesenteroides subsp. mesenteroides. The purified rEPS, designated as rEPS414, had a uniform molecular weight of 7.757 × 10⁵ Da. Analysis of the monosaccharide composition revealed that the molecule was mainly composed of glucose. The Fourier transform-infrared spectrum showed that rEPS414 contained both α-type and β-type glycosidic bonds. ¹H and ¹³C nuclear magnetic resonance spectra analysis showed that the purified rEPS contained arabinose, galactose, and rhamnose, but less uronic acid. Scanning electron microscopy demonstrated that the exopolysaccharide displayed a large number of scattered, fluffy, porous cellular network flake structures. In addition, rEPS414 exhibited strong in vitro antioxidant activity. These results showed that strain LM187 and its rEPS are promising probiotics with broad prospects in industry.

Beam-target configurations and robustness performance of the tungsten granular flow spallation target for an Accelerator-Driven Sub-critical system

Cai Han-Jie,Jia Huan,Qi Xin,Lin Ping,Zhang Sheng,Tian Yuan,Qin Yuanshuai,Zhang Xunchao,Yang Lei,He Yuan 한국원자력학회 2022 Nuclear Engineering and Technology Vol.54 No.7

The dense granular flow spallation target is a new target concept proposed for an Accelerator-Driven Sub-critical (ADS) system. In this paper, the beam-target configurations of a tungsten granular flow target for the ADS with a thermal power of 1 GW is explored. The beam profile options using different scanning methods are discussed. The critical geometry parameters are adjusted to investigate the performance of the granular target from the aspects of neutron efficiency, stability and temperature distribution in target medium. To figure out how the target under accident conditions would behave, different clogging conditions are induced in the simulation. The dynamic processes are analyzed and some important parameters such as abnormal temperature rise and beam cutoff time window are obtained. The response of the sub-critical reactor to a clogging accident is also investigated. It is indicated that the monitoring of the granular flow by the neutron detectors in the sub-critical core will be effective

A national survey on how to improve traditional Chinese medicine learning internationally: Perceptions from both teachers and students

Zhu Yu-Hang,Yan Wu,Hao Zhang,Yanfei Zhao,Yule Ren,Wei Hu,Pan Li,Huiyi Wang,Ying Wang,Boda Zhang,Yujie Wang,Hongwen Yuan,Jiping Zhang,Wenqiang Li,Yufang Zhao,Jie Zhao,Yedong Shi,Yanye Shu,Xiao Zhang,Ya 한국한의학연구원 2022 Integrative Medicine Research Vol.11 No.4

Background With the increasing popularity of traditional Chinese medicine (TCM) by the global community, how to teach basic knowledge of TCM to international students and improve the teaching quality are important issues for teachers of TCM. The present study was to analyze the perceptions from both students and teachers on how to improve TCM learning internationally. Methods A cross-sectional national survey was conducted at 23 universities/colleges across China. A structured, self-reported on-line questionnaire was administered to 34 Chinese teachers who taught TCM course in English and to 1016 international undergraduates who were enrolled in the TCM course in China between 2017 and 2021. Results Thirty-three (97.1%) teachers and 900 (88.6%) undergraduates agreed Chinese culture should be fully integrated into TCM courses. All teachers and 944 (92.9%) undergraduates thought that TCM had important significance in the clinical practice. All teachers and 995 (97.9%) undergraduates agreed that modern research of TCM is valuable. Thirty-three (97.1%) teachers and 959 (94.4%) undergraduates thought comparing traditional medicine in different countries with TCM can help the students better understand TCM. Thirty-two (94.1%) teachers and 962 (94.7%) undergraduates agreed on the use of practical teaching method with case reports. From the perceptions of the undergraduates, the top three beneficial learning styles were practice (34.3%), teacher's lectures (32.5%), case studies (10.4%). The first choice of learning mode was attending to face-to-face teaching (82.3%). The top three interesting contents were acupuncture (75.5%), Chinese herbal medicine (63.8%), and massage (55.0%). Conclusion To improve TCM learning among international undergraduates majoring in conventional medicine, integration of Chinese culture into TCM course, comparison of traditional medicine in different countries with TCM, application of the teaching method with case reports, and emphasization of clinical practice as well as modern research on TCM should be fully considered.

Identification and Functional Analysis of the Chain Length Determinant Gene ste8 Involved in the Biosynthesis of Ebosin by Streptomyces sp.139

( Zhang Yang ),( Xiao Hua Li ),( Xiao Qaing Qi ),( Jun Jie Shan ),( Rong Jiang ),( Lian Hong Guo ),( Ren Zhang ),( Yuan Li ) 한국미생물 · 생명공학회 2013 Journal of microbiology and biotechnology Vol.23 No.11

Ebosin, a novel exopolysaccharide produced by Streptomyces sp. 139, has obvious antirheumatic arthritis activity in vivo, and its biosynthesis gene cluster (ste), consisting of 27 open reading frames, has been identified. This paper reports our study of the gene functionality of ste8, the predicted protein product of which is homologous to some bacterial chain length determinant Wzz proteins. For characterization of Ste8, ste8 was cloned and expressed in the mutant strain E. coli 086:H2 (Δwzz). The functional complementation of wzz by ste8 was demonstrated by the restoration of wild-type lipopolysaccharide biosynthesis and increased levels of serum resistance of E. coli 086:H2 (Δwzz) (pET30a-ste8). To examine the function of ste8 in ebosin biosynthesis, the gene was knocked out with a double crossover via homologous recombination. The molecular weight of the ebosin derivative EPS-8m produced by the mutant Streptomyces sp. 139 (ste8-) was much lower than that of ebosin, and the binding activity of EPS-8m for IL-1R decreased significantly compared with ebosin. These results demonstrate that ste8 encodes a chain length determinant (Wzz) that functions in ebosin biosynthesis.

Preliminary Report on the Breeding of Robust and Resistant-NPV and High Quality Silkworm Race "Shengming No.1" for Summer-autumn Rearing

( Yuan Zhao ),( Ke Pin Chen ),( Qing Yao ),( Yang Chun Wu ),( Jian Zhang ),( Xi Jie Guo ) 한국잠사학회 2006 International Journal of Industrial Entomology Vol.13 No.2

Seveval Chinese and Japanese varieties with good characters were used in the breeding. After 5 years (15 generations), a pair of robust and high quality silkworm variety with NPV resistance was bred by means of a combination of crossing and pedigree selection complemented by the selection of NPV resistance. The variety was identified jointly nationwide in 2003 and 2004, and appraised by National Mulberry and Silkworm Appraising Committee. Results are as follows: its cocooning rate is over 93%, shell rate 23-25%, filament length 1200-1300 meters, reelability 75-88%, Length of non-broken cocoon filament 900-1100 meters, raw silk rate 17-19%, neatness 95-97 points, and cocoon crop, cocoon shell weight and raw silk weight per 10 000 larvae is higher than those of the control variety by 7-10%, 14-19% and 14-18%, respectively. The variety is not only robust, resistant to high temperature and NPV, easy to rear, uniform in hatching, molting and maturing, but also lays more eggs, and its fecundity is high. It is suitable to rear in the Yangtze River Basin, the Yellow River basin and the Pearl River basin of China.

Gut Microbiota Alteration Influences Colorectal Cancer Metastasis to the Liver by Remodeling the Liver Immune Microenvironment

Yuan Na,Li Xiaoyan,Wang Meng,Zhang Zhilin,Qiao Lu,Gao Yamei,Xu Xinjian,Zhi Jie,Li Yang,Li Zhongxin,Jia Yitao 거트앤리버 소화기연관학회협의회 2022 Gut and Liver Vol.16 No.4

Background/Aims:This study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis. Methods: A series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis. Results: Fewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniformis were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B. vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration. Conclusions: An increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.

Simulation of an X-ray Fresnel Zone Plate with Nonideal Factors

Jie Chen,Quanping Fan,Junhua Wang,Dengpeng Yuan,Lai Wei,Qiangqiang Zhang,Junsheng Liao,Min Xu 한국광학회 2020 Current Optics and Photonics Vol.4 No.1

Fresnel zone plates have been widely used in many applications, such as x-ray telescopes, microfluorescence, and microimaging. To obtain an x-ray Fresnel zone plate, many fabrication methods, such as electron-beam etching, ion-beam etching and chemical etching, have been developed. Fresnel zone plates fabricated by these methods will inevitably lead to some nonideal factors, which have an impact on the focusing characteristics of the zone plate. In this paper, the influences of these nonideal factors on the focusing characteristics of the zone plate are studied systematically, by numerical simulations based on scalar diffraction theory. The influence of the thickness of a Fresnel zone plate on the absolute focusing efficiency is calculated for a given incident x-ray’s wavelength. The diffraction efficiency and size of the focal spot are calculated for different incline angles of the groove. The simulations of zone plates without struts, with regular struts, and with random struts are carried out, to study the effects of struts on the focusing characteristics of a zone plate. When a Fresnel zone plate is used to focus an ultrashort x-ray pulse, the effect of zone-plate structure on the final pulse duration is also discussed.

Seismic behaviors of ring beams joints of steel tube-reinforced concrete column structure

Yingying Zhang,Jianing Pei,Yuan Huang,Ke Lei,Jie Song,Qilin Zhang 국제구조공학회 2018 Steel and Composite Structures, An International J Vol.27 No.4

This paper presents the seismic behaviors and restoring force model of ring beam joints of steel tube-reinforced concrete column structure under cyclic loading. First, the main failure mode, ultimate bearing capacity, stiffness degradation and energy dissipation capacity are studied. Then, the effects of concrete grade, steel grade, reinforcement ratio and radius-to-width ratios are discussed. Finally, the restoring force model is proposed. Results show that the ring beam joints of steel tube-reinforced concrete column structure performs good seismic performances. With concrete grade increasing, the ultimate bearing capacity and energy dissipation capacity increase, while the stiffness degradation rates increases slightly. When the radius-width ratio is 2, with reinforcement ratio increasing, the ultimate bearing capacity decreases. However, when the radius-to-width ratios are 3, with reinforcement ratio increasing, the ultimate bearing capacity increases. With radius-to-width ratios increasing, the ultimate bearing capacity decreases slightly and the stiffness degradation rate increases, but the energy dissipation capacity increases slightly.